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05-06-2022 | ASCO 2022 | Conference coverage | News

More support from COSMIC-021 for cabozantinib–atezolizumab potential in advanced UC

Author: Shreeya Nanda


medwireNews: The COSMIC-021 trial has shown promising efficacy and manageable toxicity of cabozantinib plus atezolizumab for both treatment-naïve and immune checkpoint inhibitor (ICI)-treated advanced urothelial carcinoma (UC).

Speaking at the 2022 ASCO Annual Meeting, investigator Sumanta Pal (City of Hope Comprehensive Cancer Center, Duarte, California, USA) explained that previous results from the multicohort phase 1b study have pointed to the promise of the combination for patients with locally advanced or metastatic UC who have progressed on platinum-based chemotherapy (cohort 2).

Sumanta Pal outlines results from three cohorts of the COSMIC-021 trial pointing to the potential of combining cabozantinib with atezolizumab in treatment-naïve and pretreated advanced urothelial cancer (2:11).

He told the audience in Chicago, Illinois, USA, that the current presentation focuses on cisplatin-ineligible (cohort 3) or eligible (cohort 4) advanced UC patients without prior systemic therapy and those who had received one prior ICI (cohort 5).

Participants in all three cohorts were given cabozantinib at a daily dose of 40 mg alongside atezolizumab 1200 mg every 3 weeks, which led to an objective response rate of 20% among the 30 cisplatin-ineligible patients, 30% for the 30 cisplatin-eligible patients, and 10% among the 31 ICI-treated patients during a median follow-up of 27.9, 19.1, and 32.9 months, respectively.

The complete response rates in the three cohorts were 3%, 7%, and 0%, respectively, and the partial response rates were 17%, 23%, and 10%.

A further 60% of cisplatin-ineligible and 33% of cisplatin-eligible patients as well as 52% of those who had received prior ICI therapy had stable disease, which gave corresponding disease control rates of 80%, 63%, and 61%.

The median progression-free survival was 5.6 months in the cisplatin-ineligible cohort, 7.8 months for the cisplatin-eligible cohort, and 3.0 months for the ICI-treated cohort, while the respective median overall survival durations were 14.3, 13.5, and 8.2 months.

Pal also presented safety data for the three cohorts, noting that treatment-related adverse events (TRAEs) of grade 3 or 4 occurred in 63%, 43%, and 45% of participants, respectively.

The most frequently observed grade 3–4 TRAE was amylase increase (7%) among cisplatin-ineligible patients, alanine aminotransferase increase (10%) among those who were cisplatin eligible, and amylase increase and fatigue (each in 6%) among ICI-treated patients.

There were no grade 5 TRAEs in any cohort.

AEs leading to cabozantinib dose reductions ranged from 27% in the cisplatin-eligible cohort to 43% in the cisplatin-ineligible cohort, while 40–63% of participants had an atezolizumab dose delay. A total of 13% of cisplatin-ineligible patients discontinued both study drugs due to TRAEs, as did 17% of cisplatin-eligible and 19% of ICI-treated patients.

The discussant for the presentation – Shilpa Gupta, from the Taussig Cancer Institute in Cleveland, Ohio, USA – said “this study provides hypothesis generating data” with the cabozantinib–atezolizumab combination, adding that “biomarker analysis will be very crucial to inform future combinations.”

Gupta continued: “The low rates of progressive disease and disease control rates make it an attractive option for [the] maintenance setting.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

This independent news story was supported by an educational grant from Pfizer and Merck Healthcare KGaA, Darmstadt, Germany

2022 ASCO Annual Meeting; Chicago, Illinois, USA: 3–7 June